OVERALL ABSTRACT This is a revised application requesting resources to create a NIDA P30 Core Center of Excellence Program at the University of Pennsylvania focused on studying the neurobiology of opiate use disorders (OUDs). This new center will focus on Positron Emission Tomography (PET) studies in patients seeking treatment at the Center for the Studies of Addiction (CSA) at the Perelman School of Medicine. The University of Pennsylvania has a long history in two key areas that serve as the foundation of this P30 Center of Excellence, the development of novel strategies for the opiate use disorders, and PET imaging studies of brain function. The name of the proposed center is the Penn PET Addiction Center of Excellence (Penn PACE), and represents a collaborative effort between the Departments of Radiology and Psychiatry at Penn. A key addition to this revised application is the inclusion of Yale University in this P30 Center. The center will initially focus on opioid receptors in opioid sensitivity, addiction, and suicide, and the role of oxidative stress and neuroinflammation in OUDs. This center takes advantage of unique resources at both the University of Pennsylvania and Yale University. The PIs of the Center are Dr. Robert H. Mach, the Britton Chance Professor of Radiology, Dr. Henry Kranzler, the Benjamin Rush Professor of Psychiatry, and Dr. Caryn Lerman, the John Glick Professor of Psychiatry and Vice Dean for Strategic Initiatives at Penn. Another key person is Dr. Richard Carson of the Yale University PET Center; Dr. Carson will lead the research effort at Yale University and direct the data analysis component of the Imaging Core. He is also the Co-Director of the Imaging Core with Dr. David Mankoff at Penn. The center consists of an Administrative Core and three research cores: Radiochemistry, Imaging and Clinical Core. Central to this center is the Pilot Project Core, which consists of a panel of identified and potential pilot projects by NIDA-funded investigators who use the opportunities provided by this P30 Core Center of Excellence Program to expand their research programs. We anticipate that the Penn PACE will lead to a significant advance in our understanding of the neurobiological mechanisms of opiate use disorders and neuroinflammation in a manner only possible through the combination of tightly-controlled clinical trials coupled with the unique molecular imaging properties provided by PET.